scholarly journals Novel Insights into the Effect of Hyperforin and Photodynamic Therapy with Hypericin on Chosen Angiogenic Factors in Colorectal Micro-Tumors Created on Chorioallantoic Membrane

2019 ◽  
Vol 20 (12) ◽  
pp. 3004 ◽  
Author(s):  
Martin Majerník ◽  
Rastislav Jendželovský ◽  
Marián Babinčák ◽  
Ján Košuth ◽  
Juraj Ševc ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Experimental Model ◽  
Metabolic Activity ◽  
Chorioallantoic Membrane ◽  
Angiogenic Factors ◽  
Angiogenic Factor ◽  
Treatment Modalities ◽  
Cell Models ◽  
Gene And Protein Expression ◽  
Factor Expression

Photodynamic therapy with hypericin (HY-PDT) and hyperforin (HP) could be treatment modalities for colorectal cancer (CRC), but evidence of their effect on angiogenic factors in CRC is missing. Convenient experimental model utilization is essential for angiogenesis research. Therefore, not only 2D cell models, but also 3D cell models and micro-tumors were used and compared. The micro-tumor extent and interconnection with the chorioallantoic membrane (CAM) was determined by histological analyses. The presence of proliferating cells and HY penetration into the tumor mass were detected by fluorescence microscopy. The metabolic activity status was assessed by an colorimetric assay for assessing cell metabolic activity (MTT assay) and HY accumulation was determined by flow cytometry. Pro-angiogenic factor expression was determined by Western blot and quantitative real-time polymerase chain reaction (RT-qPCR). We confirmed the cytotoxic effect of HY-PDT and HP and showed that their effect is influenced by structural characteristics of the experimental model. We have pioneered a method for analyzing the effect of HP and cellular targeted HY-PDT on pro-angiogenic factor expression in CRC micro-tumors. Despite the inhibitory effect of HY-PDT and HP on CRC, the increased expression of some pro-angiogenic factors was observed. We also showed that CRC experimental micro-tumors created on quail CAM could be utilized for analyses of gene and protein expression.

scholarly journals VEGF Regulation of Angiogenic Factors via Inflammatory Signaling in Myeloproliferative Neoplasms

2021 ◽  
Vol 22 (13) ◽  
pp. 6671
Author(s):  
Tijana Subotički ◽  
Olivera Mitrović Ajtić ◽  
Emilija Živković ◽  
Miloš Diklić ◽  
Dragoslava Đikić ◽  
...  
Keyword(s):  
Protein Expression ◽  
Chronic Inflammation ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Angiogenic Factors ◽  
Mtor Signaling ◽  
Angiogenic Factor ◽  
Inflammatory Signaling ◽  
Gene And Protein Expression ◽  
Hel Cells

Background: Chronic inflammation has been recognized in neoplastic disorders, including myeloproliferative neoplasm (MPN), as an important regulator of angiogenesis. Aims: We investigated the influence of vascular endothelial growth factor (VEGF) and pro-inflammatory interleukin-6 (IL-6) on the expression of angiogenic factors, as well as inflammation-related signaling in mononuclear cells (MNC) of patients with MPN and JAK2V617F positive human erythroleukemic (HEL) cells. Results: We found that IL-6 did not change the expression of angiogenic factors in the MNC of patients with MPN and HEL cells. However, IL-6 and the JAK1/2 inhibitor Ruxolitinib significantly increased angiogenic factors—endothelial nitric oxide synthase (eNOS), VEGF, and hypoxia-inducible factor-1 alpha (HIF-1α)—in patients with polycythemia vera (PV). Furthermore, VEGF significantly increased the expression of HIF-1α and eNOS genes, the latter inversely regulated by PI3K and mTOR signaling in the MNC of primary myelofibrosis (PMF). VEGF and inhibitors of inflammatory JAK1/2, PI3K, and mTOR signaling reduced the eNOS protein expression in HEL cells. VEGF also decreased the expression of eNOS and HIF-1α proteins in the MNC of PMF. In contrast, VEGF increased eNOS and HIF-1α protein expression in the MNC of patients with PV, which was mediated by the inflammatory signaling. VEGF increased the level of IL-6 immunopositive MNC of MPN. In summary, VEGF conversely regulated gene and protein expression of angiogenic factors in the MNC of PMF, while VEGF increased angiogenic factor expression in PV mediated by the inflammation-related signaling. Conclusion: The angiogenic VEGF induction of IL-6 supports chronic inflammation that, through positive feedback, further promotes angiogenesis with concomitant JAK1/2 inhibition.

scholarly journals Mutual influence of selenium nanoparticles and FGF2-STAB® on biocompatible properties of collagen/chitosan 3D scaffolds: in vitro and ex ovo evaluation

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Johana Muchová ◽  
Vanessa Hearnden ◽  
Lenka Michlovská ◽  
Lucie Vištejnová ◽  
Anna Zavaďáková ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Metabolic Activity ◽  
Mutual Influence ◽  
Chorioallantoic Membrane ◽  
Antagonistic Effect ◽  
Dermal Fibroblasts ◽  
Selenium Nanoparticles ◽  
Freeze Dried ◽  
Chitosan Scaffolds

AbstractIn a biological system, nanoparticles (NPs) may interact with biomolecules. Specifically, the adsorption of proteins on the nanoparticle surface may influence both the nanoparticles' and proteins' overall bio-reactivity. Nevertheless, our knowledge of the biocompatibility and risk of exposure to nanomaterials is limited. Here, in vitro and ex ovo biocompatibility of naturally based crosslinked freeze-dried 3D porous collagen/chitosan scaffolds, modified with thermostable fibroblast growth factor 2 (FGF2-STAB®), to enhance healing and selenium nanoparticles (SeNPs) to provide antibacterial activity, were evaluated. Biocompatibility and cytotoxicity were tested in vitro using normal human dermal fibroblasts (NHDF) with scaffolds and SeNPs and FGF2-STAB® solutions. Metabolic activity assays indicated an antagonistic effect of SeNPs and FGF2-STAB® at high concentrations of SeNPs. The half-maximal inhibitory concentration (IC50) of SeNPs for NHDF was 18.9 µg/ml and IC80 was 5.6 µg/ml. The angiogenic properties of the scaffolds were monitored ex ovo using a chick chorioallantoic membrane (CAM) assay and the cytotoxicity of SeNPs over IC80 value was confirmed. Furthermore, the positive effect of FGF2-STAB® at very low concentrations (0.01 µg/ml) on NHDF metabolic activity was observed. Based on detailed in vitro testing, the optimal concentrations of additives in the scaffolds were determined, specifically 1 µg/ml of FGF2-STAB® and 1 µg/ml of SeNPs. The scaffolds were further subjected to antimicrobial tests, where an increase in selenium concentration in the collagen/chitosan scaffolds increased the antibacterial activity. This work highlights the antimicrobial ability and biocompatibility of newly developed crosslinked collagen/chitosan scaffolds involving FGF2-STAB® and SeNPs. Moreover, we suggest that these sponges could be used as scaffolds for growing cells in systems with low mechanical loading in tissue engineering, especially in dermis replacement, where neovascularization is a crucial parameter for successful skin regeneration. Due to their antimicrobial properties, these scaffolds are also highly promising for tissue replacement requiring the prevention of infection.

scholarly journals An Efficient Photodynamic Therapy Treatment for Human Pancreatic Adenocarcinoma

2020 ◽  
Vol 9 (1) ◽  
pp. 192 ◽  
Author(s):  
Alexandre Quilbe ◽  
Olivier Moralès ◽  
Martha Baydoun ◽  
Abhishek Kumar ◽  
Rami Mustapha ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Photodynamic Therapy ◽  
Immune System ◽  
Cancer Cells ◽  
Pancreatic Adenocarcinoma ◽  
Cell Lines ◽  
Folate Receptor ◽  
Mice Model ◽  
Gene And Protein Expression ◽  
The Impact

To date, pancreatic adenocarcinoma (ADKP) is a devastating disease for which the incidence rate is close to the mortality rate. The survival rate has evolved only 2–5% in 45 years, highlighting the failure of current therapies. Otherwise, the use of photodynamic therapy (PDT), based on the use of an adapted photosensitizer (PS) has already proved its worth and has prompted a growing interest in the field of oncology. We have developed a new photosensitizer (PS-FOL/PS2), protected by a recently published patent (WO2019 016397-A1, 24 January 2019). This photosensitizer is associated with an addressing molecule (folic acid) targeting the folate receptor 1 (FOLR1) with a high affinity. Folate binds to FOLR1, in a specific way, expressed in 100% of ADKP or over-expressed in 30% of cases. The first objective of this study is to evaluate the effectiveness of this PS2-PDT in four ADKP cell lines: Capan-1, Capan-2, MiapaCa-2, and Panc-1. For this purpose, we first evaluated the gene and protein expression of FOLR1 on four ADKP cell lines. Subsequently, we evaluated PS2’s efficacy in our cell lines and we assessed the impact of PDT on the secretome of cancer cells and its impact on the immune system. Finally, we evaluate the PDT efficacy on a humanized SCID mouse model of pancreatic cancer. In a very interesting way, we observed a significant increase in the proliferation of activated-human PBMC when cultured with conditioned media of ADKP cancer cells subjected to PDT. Furthermore, to evaluate in vivo the impact of this new PS, we analyzed the tumor growth in a humanized SCID mice model of pancreatic cancer. Four conditions were tested: Untreated, mice (nontreated), mice with PS (PS2), mice subjected to illumination (Light only), and mice subjected to illumination in the presence of PS (PDT). We noticed that the mice subjected to PDT presented a strong decrease in the growth of the tumor over time after illumination. Our investigations have not only suggested that PS2-PDT is an effective therapy in the treatment of PDAC but also that it activates the immune system and could be considered as a real adjuvant for anti-cancer vaccination. Thus, this new study provides new treatment options for patients in a therapeutic impasse and will provide a new arsenal in the fight against PDAC.

scholarly journals A Mathematical Model of anIn VitroExperiment to Investigate Endothelial Cell Migration

2002 ◽  
Vol 4 (4) ◽  
pp. 251-270 ◽  
Author(s):  
M. J. Plank ◽  
B. D. Sleeman ◽  
P. F. Jones
Keyword(s):  
Mathematical Model ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Blood Vessels ◽  
Three Dimensional ◽  
Cell Movement ◽  
Quantitative Model ◽  
Angiogenic Factors ◽  
Endothelial Cell Migration ◽  
Angiogenic Factor

Angiogenesis, the growth of new blood vessels from existing ones, is an important, yet not fully understood, process and is involved in diseases such as rheumatoid arthritis, diabetic retinopathy and solid tumour growth. Central to the process of angiogenesis are endothelial cells (EC), which line all blood vessels, and are capable of forming new capillaries by migration, proliferation and lumen formation. We construct a cell-based mathematical model of an experiment (Vernon, R.B. and Sage, E.H. (1999) “A novel, quantitative model for study of endothelial cell migration and sprout formation within three-dimensional collagen matrices”,Microvasc. Res.57, 118–133) carried out to assess the response of EC to various diffusible angiogenic factors, which is a crucial part of angiogenesis. The model for cell movement is based on the theory of reinforced random walks and includes both chemotaxis and chemokinesis. Three-dimensional simulations are run and the results correlate well with the experimental data. The experiment cannot easily distinguish between chemotactic and chemokinetic effects of the angiogenic factors. We, therefore, also run two-dimensional simulations of a hypothetical experiment, with a point source of angiogenic factor. This enables directed (gradient-driven) EC migration to be investigated independently of undirected (diffusion-driven) migration.

scholarly journals Vascular Effects of Photodynamic Therapy with Curcumin in a Chorioallantoic Membrane Model

2019 ◽  
Vol 20 (5) ◽  
pp. 1084 ◽  
Author(s):  
Hilde Buzzá ◽  
Lucas Fialho de Freitas ◽  
Lilian Moriyama ◽  
Ramon Teixeira Rosa ◽  
Vanderlei Bagnato ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Molecular Oxygen ◽  
Chorioallantoic Membrane ◽  
Topical Administration ◽  
Inhibitory Effect ◽  
Vascular Effects ◽  
Vascular Effect ◽  
Chick Chorioallantoic Membrane ◽  
Anti Oxidant ◽  
Total Fluence

Photodynamic Therapy (PDT) is a treatment that requires light, a photosensitizing agent, and molecular oxygen. The photosensitizer is activated by light and it interacts with the oxygen that is present in the cellular microenvironment. The molecular oxygen is transformed into singlet oxygen, which is highly reactive and responsible for the cell death. Therefore, PS is an important element for the therapy happens, including its concentration. Curcumin is a natural photosensitizer and it has demonstrated its anti-inflammatory and anti-oxidant effects that inhibit several signal transduction pathways. PDT vascular effects of curcumin at concentrations varying from 0.1 to 10 mM/cm2 and topical administration were investigated in a chick Chorioallantoic Membrane (CAM) model. The irradiation was performed at 450 nm, irradiance of 50 mW/cm2 during 10 min, delivering a total fluence of 30 J/cm2. The vascular effect was followed after the application of curcumin, with images being obtained each 30 min in the first 3 h, 12 h, and 24 h. Those images were qualitatively and quantitatively analyzed with a MatLAB®. Curcumin was expected to exhibit a vascular effect due to its angio-inhibitory effect. Using curcumin as photosensitizer, PDT induced a higher and faster vascular effect when compared to the use of this compound alone.

scholarly journals Angiogenesis and Diabetes: Different Responses to Pro-Angiogenic Factors in the Chorioallantoic Membrane Assay

2008 ◽  
Vol 14 (11-12) ◽  
pp. 705-714
Author(s):  
Giovana S. Di Marco ◽  
Antoine Alam ◽  
Frédéric Dol ◽  
Pierre Corvol ◽  
Jean-Marie Gasc ◽  
...  
Keyword(s):  
Chorioallantoic Membrane ◽  
Angiogenic Factors ◽  
Chorioallantoic Membrane Assay

The role of periodontal treatment associated with photodynamic therapy on the modulation of systemic inflammation in the experimental model of asthma and periodontitis

2020 ◽  
Vol 29 ◽  
pp. 101619 ◽  
Author(s):  
Felipe Murakami-Malaquias-da-Silva ◽  
Ellen Perim Rosa ◽  
Jessica Gonzaga Oliveira ◽  
Isabella Sena Avelar ◽  
Marlon Palma-Cruz ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Experimental Model ◽  
Systemic Inflammation ◽  
Periodontal Treatment
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